The rate of proliferation of hematopoietic stem cells (HSC) is regulated by at least three separate factors: 1) Specialized stromal cells which are essential for supporting the growth of HSC in any particular site; 2) cell-cell interaction with other cells in the site, which inhibit their growth locally; and 3) hormonal factors which mediate the response of HSC in uninvolved sites to depletion of the body's HSC population elsewhere. Experiments are proposed to ascertain the relative contribution of each of these mechanisms to the control of the HSC proliferation. The role of stromal factors will be assayed by measuring the growth of colony forming units (CFU's) in femurs and spleens implanted subcutaneously into normal host mice. The relative role of long-range (humoral) regulatory factors and short-range (cell-cell interactions) ones will be assessed by comparing the growth of implanted CFU in both femurs of mice which had previously been exposed to 300 rads with one leg shielded. The effects of androgens, estrogens, and plasma obtained from irradiated mice on HSC proliferation will also be studied.